This invention relates to mixtures of oxidants which are referred to in this specification as “super-oxidized water,” a term which is known in the art.
Super-oxidized water may be used as a sterilizing, disinfecting and biocidal solution. One form of super-oxidized water is produced by the applicant under the trademark STERILOX®. This STERILOX super-oxidized water is generated at the point of use, for example in a hospital, by passing saline solution over coated titanium electrodes separated by a semi-permeable ceramic membrane at a current of about 6 to 9 Amps. An apparatus having coated titanium electrodes separated by a semi-permeable ceramic membrane is disclosed in the specifications of UK Patent Nos. 2253860 and 2274113. The basic structure of the apparatus is disclosed in GB2253860 and can be used to produce the STERILOX super-oxidized water.
STERILOX super-oxidized water contains a mixture of oxidizing species, predominantly hypochlorous acid (HOCl) and sodium hypochlorite. The STERILOX super-oxidized water has a pH of 5-7 and an oxidation reduction potential (redox) of around 1000 mV. The high redox potential allows for the quick and efficient destruction of microbes (bacteria, viruses, fungi and spores). Hypochlorous acid and hypochlorite are in equilibrium and the position of the equilibrium is determined solely by the pH.
Applicant has found that the resultant super-oxidized water is non-hazardous, non-irritating and non-sensitizing to the skin, non-irritating to the eyes, not harmful if swallowed and shows no evidence of mutagenic activity.
It is considered that hypochlorous acid exerts its biocidal effect by attacking the surface and plasma membrane proteins, impairing transport of solutes and the salt balance of bacterial cells (Pieterson et al, Water SA, 22(1): 43-48 (1996)). However, it is believed that HOCl does not enter freely into eukaryotic cells, which may explain the selectivity of hypochlorous solutions.
The STERILOX process produces an extremely effective sterilizing, cold, non-toxic solution, which is free from highly toxic chemicals and acts against a wide variety of bacteria, fungi, viruses and spores. The generation of STERILOX solutions requires only water, electricity and pure, vacuum-dried crystalline salt. Applicant considers that the STERILOX super-oxidized water will be suitable for a broad range of applications in both medical and non-medical environments, such as the preservation of poultry and fish and general agricultural and petrochemical uses, the breaking down of bacterial biofilm, water treatment and general disinfection in medical and veterinary applications. The STERILOX super-oxidized water has been found to be particularly useful for the disinfection of endoscopes which are sensitive to other cold disinfectants, such as peracetic acid, which are commonly used.
While glutaraldehyde may be used as a reliable disinfecting agent of flexible fiber-optic endoscopes and other heat-sensitive instruments, although being widely practiced in many hospitals, its use can cause asthma and dermatitis in healthcare staff as a result of exposure to glutaraldehyde fumes, hence a predilection to the use of peracetic acid and the relatively recent move towards the use of STERILOX super-oxidized water in such applications.
STERILOX super-oxidized water has been tested and is the subject of two scientific papers by Selkon et al, Journal of Hospital Infection, 41: 59-70 (1999) and Shetty et al, Journal of Hospital Infection, 41: 101-105 (1999). In these studies, freshly produced STERILOX super-oxidized water was found to be highly active against Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, Mycobacterium chelonae, Escherichia coli (including type 0157), Enterococcus faecalis, Pseudomonas aeruginosa, Bacillus subtilis var niger spores, methicillin-resistant Staphylococcus aureus, Candida albicans, poliovirus type 2 and human immunodeficiency virus HIV-1.
There has been a recent upsurge in interest in the use of super-oxidized water as a disinfectant, because of its rapid and highly biocidal activity against a wide range of bacteria. Tanaka et al, Journal of Hospital Infection. 34: 43-49 (1996), report the electrolysis of a saline solution to produce a super-oxidized water with a highly acidic pH of 2.3-2.7, which limits its suitability for many applications, particularly the disinfection of endoscopes. The acidic pH of the super-oxidized water produced by the method described by Tanaka et al. also precludes its use in other medical indications.
Having carried out trials in a large number of applications, including those mentioned above, Applicant turned its attention to the use of STERILOX super-oxidized water as a disinfectant of mammalian tissue, in particular the treatment of open wounds such as leg ulcers.
An article by Chemy in The Prescriber (May 1996) entitled “GP guide to the care of patients with leg ulcers” states “leg ulcers are notoriously difficult to treat successfully and can seriously reduce the patient's quality of life.” Indeed, according to Chemy, “epidemiological studies have shown that at any given time there are approximately 100,000 patients in the UK that have leg ulceration. In treating these patients it has been estimated that over £39 million per year alone is spent on materials used in their ulcer care.”
There are two types of leg ulcers: arterial and venous. Arterial ulcers, which are much harder to treat, are caused by ischemia, while venous ulcers are caused by blood stasis in the veins.
There are many proposals for the management of ulcers, all of which have varying degrees of success. Successful ulcer management is very much dependent on the rigid adherence to a program of treatment in combination with effective disinfection of the wound, which reduces bacterial infection and promotes the regeneration of dermal fibroblasts and keratinocytes in the bed of the ulcer which are essential for healing of the wound and the growth of new tissue. If the bacterial growth is not controlled, the wound cannot heal.
The most useful treatment for venous ulcers is the use of compression bandages together with elevation of the leg(s). This mimics the pumping action of the calf muscles which return the blood back to the body and maximizes the removal of blood from the leg(s). In conjunction with this, other treatment strategies include the use of topical treatments such as GRANUFLEX® to aid granulation and skin repair, alginates to clean the wound of debris, dry inert dressings to protect the wound (but which do not promote healing), and bacteriostatic or bactericidal ointments to reduce the infection. While antibiotics have been used to reduce infection in the past, nowadays this is not a treatment of choice due to the increased risk of antibiotic resistance.
While potassium permanganate (KMnO4) is an oxidant which has stood the test of time in the treatment of leg ulcers, it still nevertheless has the disadvantages of irritating and injuring newly grown skin and causing skin discoloration. Known hypochlorites, such as EUSOL (Edinburgh University Solution of Lime) and Daikin's solution, rely on a high concentration of hypochlorite ions for their disinfectant properties. In fact, these compounds are no longer recommended for use due to their irritant and painful effects and impairment of cell growth which outweigh their therapeutic value, resulting in these preparations falling out of use. Attempts have been made to reduce the alkaline effect of the high hypochlorite ion content of these Solutions, e.g. by the use of suitable buffers, but have been found to be ineffective in such circumstances.
All this has militated against the use of preparations including hypochlorites for the treatment of leg ulcers. However, the success in disinfection and sterilization of endoscopes and the known non-irritant effects of the STERILOX super-oxidized water, have led the Applicant to re-address the treatment of open wounds such as leg ulcers.